Background and Objectives: Graft-versus-host disease (GVHD) is one of life-threatening post-transplantation complications. Several recent studies have described a significant correlation between transplantation outcome and three single nucleotide polymorphisms (SNPs) in the NOD2 gene. This study was conducted to evaluate the association of NOD2 gene polymorphisms with the occurrence of GVHD in acute myelogenous leukemia patients who underwent HSCT from their HLA-matched sibling donors.Materials and Methods: We examined retrospectively NOD2 genotypes by PCR-SSP both in 124 patients who underwent HSCT and in their donors; then, the association of the genetic polymorphisms on acute and chronic GVHD was evaluated. Median follow up of patients was 40 months (range of 28-77 months). Statistical analyses were performed using Chi-square test and SPSS software. Results: Mutation incidence was the same between donors and recipients as 12.1%. In three of the patient-donor pairs (2.4%) SNPs occurred in both resulting in an overall frequency of 21.8% in patient-donor pairs. There weren’t any significant differences between aGVHD and cGVHD incidence rates when donor/recipient pairs with SNPs were compared with the pairs without SNPs. aGVHD and cGVHD incidence rates in the former pairs were 52% and 56% and in the latter pairs 50.5% and 55%, respectively.Conclusions: No impact of NOD2 SNPs on incidence of acute and chronic GVHD was observed. Further studies are required to ascertain whether the findings of this study can be extended to other disease groups. In addition, further studies are required to identify the relevance of other SNPs.